In the NaCl deprived rat, we have demonstrated that chronic dietary loading with NaI, NaHCO3, Na acetate (Ac), Na thiocyanate (SCN), NaNO3, and KHCO3 all failed to inhibit plasma renin activity (PRA), whereas PRA was inhibited by NaCl, KCl, and NaBr. Despite negative Na ion balance, choline chloride but not choline bicarbonate loading inhibited renin. Acute NaHCO3 infusion also failed to inhibit renin. The purpose of the present study is to further evaluate the role of Cl ion in the regulation of renin, both in the rat and in man. NaCl deprived rats will receive an acute infusion of NaCl, NaAc, NaBr, NaI, KCl, KHCO3 choline chloride or choline bicarbonate. PRA will be measured before and after expansion. PRA will also be measured after oral loading with NaCl and NaHCO3 in NaCl deprived normotensive human subjects. To futher evaluate the role of Cl ion , PRA will be compared in control rats and rats that are selectively Cl depleted. Both furosemide and K ion depletion inhibit Cl ion transport in the loop of Henle. If inhibition of PRA by NaCl, KCl, NaBr, and choline chloride is related to NaCl transport, no inhibition would be anticipated in the furosemide treated or K ion depleted animals; PRA will be measured after acute expansion with NaCl, KCl, NaBr, and choline chloride in furosemide treated and separate groups of potassium depleted rats. To determine if inhibition of renin by NaBr and choline chloride is dependent upon tubular flow, in the dog, the renin responses to renal arterial infusion of these salts will be compared in the intact kidney and in the non-filtering kidney. In apparent contrast to whole animal studies, retrograde microperfusion experiments suggest that NaCl transport across the macula densa stimulates rather than inhibits single nephron renin. To evaluate the hypothesis that increased single nephron renin may reflect acute inhibition of release, renin secretion rates and single nephron renin will be measured serially before, during and after acute volume expansion with NaCl and NaHCO3. The results of this study should provide basic information about mechanisms of renin release. Clinically, this may become relevant to the understanding of "inappropriate" renin release in selected hypertensive and renal diseases.